Hyperpolarized [U-2H, U-13C]Glucose Reports on Glycolytic and Pentose Phosphate Pathway Activity in EL4 Tumors and Glycolytic Activity in Yeast Cells.

Purpose: A resonance at ~181 ppm in the ¹³C spectra of tumors injected with hyperpolarized [U-²H, U-¹³C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG ¹³C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) Methods: Tumor-bearing mice were injected with ¹³C₆ glucose and the ¹³C-labeled and total 6PG and 3PG concentrations measured. ¹³C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1D) and wild-type yeast were acquired following addition of hyperpolarized [U-²H, U-¹³C]glucose and again ¹³Clabeled and total 6PGand 3PGwere measured by LC-MS/MS Results: Tumor ¹³C-6PG was more abundant than ¹³C-2PG/ 3PG and the resonance at ~181 ppm matched more closely that of 6PG. ¹³C MR spectra of wild-type and zwf1D yeast cells showed a resonance at ~181 ppm after labeling with hyperpolarized [U-²H, U-¹³C]glucose, however, there was no 6PG in zwf1D cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG Conclusion: The resonance at ~181 ppm in ¹³C MR spectra following injection of hyperpolarized [U-²H, U-¹³C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells. [ABSTRACT FROM AUTHOR]